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HX64064867 
RD651  Ew52  S^labusot  lectures 


RECAP 


15 
a:  I 


Columbia  (Hnitoem'tp 

College  of  ^tp^tetans;  anb  ^urgeonsi 


Hibrarp 


Digitized  by  tine  Internet  Arciiive 

in  2010  witii  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/syllabusoflecturOOewin 


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SYLLABUS  OF  LECTURES 


QN 


TUMORS 


BY 

JAMES  EWING,  M.D., 

DEPARTMENT   OF   PATHOLOGY 
CORNELL   UNIVERSITY    MEDICAL    COLLEGE. 


NEW    YORK   CITY, 
1902; 


1  ikfftMTii 


TUMORS. 


Definition.  A  tumor  is  an  autonomous  new  growth  of 
tissue. 

Scope  of  Term. 

Clinicall}^,  any  more  or  less  permanent  localized  swell- 
ing is  tentativel}'  called  a  tumor.  The  pathological  classi- 
fication separates  among  such  swellings. 

( 1 )  Inflammatory  Hyperplasias. 

(2)  Retention  Cysts. 

(3)  Triie  tumors.     Neoplasms. 

(1)   Inflammatory  Hyperplasia. 

Jt  has  already  heen  noted  that  a  simple  inflammatory 
process  may  produce  a  localized  increase  in  the  size  of  a 
part,  simulating  a  tumor.  Instances  of  this  sort  occur  es- 
pecially in  the  skin  and  mucous  membranes.  (Nasal 
polyps,  fungous  endometritis  and  uterine  polyps,  chronic 
prostatitis,  venereal  warts,  fungoid  growth  following  ec- 
.cenia.) 

This  increase  in  the  size  of  the  part  is  referable  to 
moderate  increase  in  the  number  and  size  of  cells,  to 
retention  of  secretion,  and  to  inflammatory  exudate.  Such 
inflammatory  hyperplasia  may,  however,  pass  by  insensible 
gradations  into  a  true  tumor  process,  and  this  fact  consti- 
tutes one  of  the  strongest  arguments  against  the  parasite 
theory  of  the  origin  of  tumors. 


(2)  Retention  Cysts. 

The  retention  of  secretion  in  occluded  glandular  alveoli 
accounts  for  much  of  the  bulk  of  many  tumors,  but  not 
infrequently  such  retained  secretion  produces  a  marked 
swelling  or  tumor  apart  from  any  true  neoplastic  process. 
It  is  commonly  seen  in  chronic  inflammations  of  glandu- 
lar structures.  {Galactocele,  one  form  of  goitre,  ranula, 
simple  and  corpus  luteum  cysts  of  ovary,  hydronephrosis, 
congenital  cystic  kidney  f) 


(3)  Neoplasms. 

This  term  applies  to  the  autonomous  new  growths  in 
which  the  process  differs  essentially  from  that  of  inflam- 
matory hyperplasia,  in  that  the  multiplication  of  cells  is 
much  greater  and  the  new  cells  produced  differ  in  type 
from  the  normal  cells  originating  the  tumor. 

The  broadest  conception  of  a  tumor  and  one  which  per- 
haps best  expresses  the  relation  of  a  tumor  to  other 
pathological  processes  and  to  the  originating  tissue  is  that 
of  a  parasitic  grozvth.  In  this  sense  a  tumor  grows  for 
itself  and  at  the  expense  of  the  harboring  tissue  and  host. 
The  parasitic  relation  is  apparent  in  certain  monsters 
where  considerable  portions  of  one  individual  are  im- 
planted in  another,  while  there  appear  to  be  all  gradations 
between  the  extreme  examples  of  parasitism,  such  as  the 
Siamese  twins,  through  the  sacral  teratomata,  dermoids, 
embryonal  tumors  of  the  genito-urinary  tract,  even  to 
the  epithelioma  of  the  lip  which  is  believed  by  some  to 
originate  from  misplaced  epithelial  cells  which  have  taken 
on  an  independent  and  parasitic  existence  (Cohnheim, 
Ribbert).  This  conception  of  the  parasitic  nature  of  tu- 
mors is  also  one  of  the  strongest  arguments  against  the 
belief  that  neoplasms  are  caused  by  the  invasion  of  the 


3 

cells  by  parasitic  microorganisms.     Thus  it  would  seem 
that  the  tumor  itself  is  the  parasite. 

Characters  of  Tumor  Cells. 

Anaplasia. 

Tumor  cells  are  usually  less  differentiated  than  their 
cells  of  origin.  They  are  usually  larger,  sometimes  smaller, 
spindle  cells  may  become  spheroidal,  but  whatever  the  de- 
gree of  change,  tumor  cells  tend  to  revert  to  the  less  dif- 
ferentiated form  of  embryonal  tissues. 

This  reversion  of  the  tumor  cells  to  the  embryonal  type 
is  one  of  the  clearest  distinctions  between  inflammatory 
and  neoplastic  processes,  and  is  called  anaplasia.  (Hanse- 
mann.) 

The  nuclei  of  tumor  cells  are  usually  larger  than  is 
normal  and  exhibit  an  abundance  of  chromatin,  features 
which  indicate  greatly  increased  power  of  growth.  On 
the  other  hand  tumors  of  specialized  epithelium  possess 
diminished  power  to  produce  special  secretions,  i.e.,  special 
power  of  physiological  function.  It  is  believed  that  one 
of  the  essential  characters  of  tumor  cells  is  an  excess  of 
the  tendency  of  growth  gained  at  the  expense  of  the 
capacity  for  function.  (Adami.)  This  physiological  fact 
should  be  included  in  the  conception  of  anaplasia. 

Metaplasia. 

In  some  tumors  the  cells  may  exhibit  distinct  differ- 
ences from  their  original  function. 

Thus,  fibroblasts  produce  bone  and  cartilage,  and  col- 
umnar epithelium  becomes  flat  and  round.  This  change 
is  called  metaplasia. 

Metaplastic  changes  are  not  indiscriminate  but  follow 


inriuences  based  on  the  embrvological  development  of  tis- 
sues. 

I'^ibroblasts  may  produce  bone  and  cartilage  because  all 
of  these  are  closely  related  mesoblastic  tissues;  but 
epithelial  cells  never  assume  the  characters  of  fibroblasts 
in  producing-  bony  or  cartilaginous  tissues. 

Cell- division. 

Tumor  cells  multiply  by  mitosis  but  instead  of  always 
dividing  equally  into  two  new  cells  three  or  more  may 
be  formed  with  varying  quantities  of  chromatin  and  pro- 
toplasm. Such  pathological  mitosis  increases  with  the 
anaplasia  and  malignancy  of  the  tumor.  Amitosis  is  also, 
to  a  less  extent,  concerned  in  the  multiplication  of  tumor 
cells.     Endogenous  cell  formation  also  occurs. 

Structure  and  Growth  of  Tumors. 

Tumor  processes  have  been  shown  to  originate  in  one 
or  many  very  small  groups  of  cells.  The  tumor  may  then 
grow  by  the  multiplication  of  these  cells  alone,  or  other 
normal  cells  may  be  steadily  excited  to  excessive  prolifera- 
tion. Thus  in  carcinoma  of  the  colon  the  edges  of  the 
growth  frequently  show  all  gradations  from  normal  glan- 
dular epithelium  through  pronounced  hypertrophy  of  epi- 
thelial cells  up  to  the  active  tumor  cells  with  excess  of 
chromatin.   - 

The  former  tendency  produces  an  encapsulated  growth, 
especially  if  benign,  {lipoma'),  or  the  tumor  cells  orig- 
inating from  a  small  focus  may  rapidly  push  their  way 
through  lymph  spaces  and  grow  to  a  large  size  in  neigh- 
boring parts.  {Carcinojiia  of  a.villary  nodes  zi'ifJi  minute 
nodules  in  breast.)  The  latter  tendency  yields  locally 
spreading  growths  with  or  without  metastasis.  (Diffuse 
carcinoma  of  colon.) 


^.S'HT^  4^*tx^^f6^  ^,  ?o 


13 


CLASSES  OF   TUMORS. 

Connective   Tissue. 

Fibrillar  connective  tissue  Fibroma 

Mucous  tissue  Myxoma 

Fat  tissue  Lipoma 

Cartilage  Chondroma 

Bone  Osteoma 

Embryonal  connective  tissue  Sarcoma 

Endothelium  Endothelioma 

Muscle  Tissue. 

Smooth  muscle  Leiomyoma 

Striated  muscle  Rhabdomyoma 

Nerve  Tissue. 

Nerve  cells  and  fibres  Neuroma 

Neuroe:lia  Glioma 


'in' 


Vessels. 

Blood  Angeioma 

Lymph  Lymphangeioma 

Epithelial  Tissue. 

Glands  Adenoma 

Epithelium,  Glandular  Carcinoma 

Epithelium,  Squamous  Epithelioma 

Skin  Dermoid 

Complex  Embryonal 

Implantations  Teratoma 


14 


FIBROMA. 

Occurrence.  Siibcutaneoits  tissue,  intermuscular  septa, 
breast,  and  other  organs. 

Cells  of  Origin.  Usually  from  fibroblasts  of  support- 
ing connective  tissue.  Or  from  fibroblasts  of  vessel 
walls,  when  many  new  vessels  and  much  endothelium  may 
accompany  the  growth.  Or  from  basement  membrane- 
cells  of  alveoli.  (Canalicular  fibroma  of  breast.)  Or 
from  fibroblasts  of  nerve  trunks. 

Structure.  That  of  fibrillated  connective  tissue.  The 
proportion  of  cells  and  fibres  varies  greatly,  the  more  cel- 
lular tumors  becoming  fibrosarcomatous  and  recurring 
locally  after  operation.  They  are  hard,  from  densely 
packed  cells  and  fibres,  or  soft,  from  excess  of  cells  and 
from  oedema. 

Varieties:  ^Multiple  fibroma  of  skin,  arises  usually 
in  nerve  trunks  and  shows  fibroblasts  mingled  with  much 
endothelium,  and  sometimes  with  nerve  fibres. 

Keloid  is  a  term  applied  to  very  dense  acellular  fibrous 
thickenings  of  scars,  with  numerous  lymph  channels,  but 
extending  beyond  them  and  following  the  line  of  blood 
channels.  It  is  possibly  of  inflammatory  origin,  but  is 
progressive,  although  not  extending  beyond  the  cutis. 
Fibrous  papilloma  is  common  on  mucous  surfaces 
and  consists  of  fibrous  tissue  and  vessels  covered  with 
hypertrophic  epithelium.  It  is  often  largely  inflamma- 
tory in  origin. 

Combinations  of  fibroma  with  other  tumors  are  very 
frequent. 


15 


i^YXOMA. 

Occurrence.  In  loose  connective  tissue  of  back,  navel, 
cheek,  vulva,  scrotum,'  mucous  surfaces,  bone  marrow, 
breast,  placental  mole,  nerve  trunks,   parotid. 

Cells  of  Origin,  fibroblasts  of  supporting  connective 
tissue,  of  basement  membranes,  of  adenoid  tissue,  of  nerve 
trunks ;  and  fat  cells. 

Structure.  Peculiar  polyhedral  cells  lying  in  a  mucin- 
ous matrix  which  shows  precipitated  basic  fibrils  and  finely 
granular  or  homogeneous  mucus.  The  proportion  of  cells 
and  mucus  varies  greatly.  The  cells  are  often  connected 
by  radiating  processes. 

Varieties:  (i)  Primary  myxoma  arises  from  embry- 
onal mucous  tissue  which  precedes  the  formation  of  con- 
nective tissue  and  fat.    This  tumor  is  rare. 

(2)  Secondary  myxoma  is  an  oedematous  fibroma  or 
lipoma  which  undergoes  mucoid  degeneration.  Such 
tumors  are  common.  It  is  usually  difficult  to  distinguish 
primary  from  secondary  myxomata. 

The  primary  myxoma  is  seen  in  the  new  born  ;  a  typ- 
ical form  in  the  hydatid  mole,  which  is  however  largely 
an  hydropic  degeneration.  Clinically  the  myxoma  of  the 
central  and  peripheral  nervous  systems  is  important.  i\[u- 
cous  polyps  of  the  nares,  etc.,  are  largely  inflammatory. 
Combinations  with  lipoma  and  sarcoma  are  frequent. 


i6 


LIPOMA. 

Occurrence.  Skin,  often  in  neck  and  back,  rarely  in 
hairy  parts.  Fasciae,  joint  capsules,  renal  capsule,  mus- 
cles (pseudo-hypertrophy),  nerves  (multiple  symmetrical 
lipomata). 

Cells  of  Origin.    Fat  cells  and  fibroblasts. 

Structure.  That  of  normal  fat  tissue,  but  the  tumor 
cells  var}'  in  size,  are  irregularly  grouped  into  uneven 
lobules,  blood  vessels  are  usually  more  abundant,  and 
fibrous  tissue  usually  excessive  or  deficient.  Growth  is 
usually  circumscribed,  but  may  be  diffuse. 

Varieties:  Combinations  are  frequent  with  myxoma, 
fibroma,  angeioma,  and  sarcoma. 


CHONDROMA. 

.  Occurrence.  One  of  the  most  widely  distributed  of  tu- 
mors, arising  from  (i)  cartilage,  bone,  or  connective  tis- 
sue; (2)  forming  frequently  in  other  tumors  of  the  con- 
nective tissue  series,  including  endothelioma,  and  (3) 
very  frequently  present  in  tumors  developed  from  mis- 
placed embryonal  remnants. 

Cells  of  Origin.  Fibroblasts,  endothelium,  bone  and 
cartilage  cells.    Embryonal  connective  tissite  cells. 

Structure.  The  type  is  usually  that  of  hyaline  cartilage, 
but  may  be  fibrous,  or  fibro-elastic.  The  cells  vary  greatly 
in  size,  number,  and  arrangement.    The  stroma  is  hyaline. 


or  fibrous,  mucoid,  or  calcific.  Blood  vessels  are  more 
numerous  than  in  normal  cartilage  but  degeneration  and 
necrosis  is   common. 

Varieties :  Combinati6ns  with  fibroma,  osteoma,  lipoma, 
myxoma,  and  sarcoma,  are  common.  The  most  peculiar 
and  striking  chondromata  are  those  that  develop  from 
misplaced  embryonal  cells,  as  along  the  vertebrae,  epiphy- 
ses, in  the  genital  organs,  parotid,  and  lung. 


OSTEOMA, 


Occurrence.  On  bone  and  periosteum,  or  in  soft  tissue 
as  a  part  or  secondary  feature  of  fibroma,  chondroma,  and 
sarcoma. 

Cells  of  Origin.  Bone  or  cartilage  cells,  and  fibro- 
blasts. 

Structure.  Dense  ivory  osteomata  show  very  few 
Haversian  canals  or  medullary  spaces,  while  spongy  os- 
teomata are  more  vascular  and  contain  numerous  medul- 
lary spaces.  The  structure  may  be  that  of  bony  tissue 
or  the  cells  may  have  comparatively  few  processes,  some- 
what resembling  cartilage  cells,  and  the  matrix  is  less 
dense  than  that  of  bone  (osteoid  tissue). 

Varieties:  Inflammatory  exostoses  are  difficult  to  sep- 
arate from  tumors.  Pure  osteomata  are  not  common  but 
are  most  frequent  about  the  cranium. 

Osteo-fibroma,  chondroma,  and  sarcoma,  are  the  usual 
types.  Osteoma  occurs,  rarely,  in  the  brain  and  lung, 
from  misplaced  embryonal  tissue.  In  the  jaw  one  variety 
is  the  odontoma,  containing  bone,  dentine,  and  enamel 
organ. 


SARCOMA. 

Definition.  A  sarcoma  is  a  malignant  tumor  developed 
from  cells  of  the  connective  tissue  series,  and  of  which  the 
cells  are  more  abundant  than  in  normal  connective  tissue 
or  in  simple  benign  tumors  of  connective  tissue,  while  the 
intercellular  substance,  although  present,  is  usually  very 
scanty.     In  these  tumors  the  anaplasia  is  pronounced. 

Occurrence.  Sarcomata  develop  wherever  the  simple 
tumors  of  the  connective  tissues  are  found.  They  are 
most  frequently  located  in  the  skin,  bones,  lymph-nodes, 

and  viscera. 

Cells  of  Origin.  The  fibroblast  and  all  its  derivatives, 
including  cartilage,  bone,  fat,  lymphoid,  and  smooth  mus- 
cle cells,  and  from  the  fibroblasts  of  blood  vessels,  nerve 
trunks,  basement  membranes,  and  interstitial  tissues. 

Cellular  endothelial  tumors  are  closely  related  to  sar- 
comata. .    . 

Structure  and  Varieties. 

(1)  Simple  Fibroblastic  Sarcoma. 

(a)  Small  and  large  spindle  cell  sarcomata  contain 
numerous  spindle  shaped  fibroblasts,  with  little  fibrillated 
inter-cellular  substance,  usually  with  very  few  blood  ves- 
sels. Some  of  these  tumors  appear  to  be  derived  from 
the  fibroblasts  or  endothelium  or  embryonal  smooth  muscle 
cells  of  many  minute  blood  vessels,  but  the  cells  exhibit 
the  characters  of  fibroblasts.  They  are  common  in  the 
skin  where  they  develop  from  nerve  trunks  and  base- 
ment membranes  of  sweat  or  sebaceous  glands  or  hair  fol- 
licles.    There  are  all  gradations  from  simple  fibroma  to 


^9 

fibroblastic    sarcoma    and    numerous    combinations    with 
other  types  of  sarcoma. 

{b)  Giant  cell  sarcoma  contains  large  and  small  giant 
cells  of  the  type  of  nVyeloplacques,  many  large  or  small 
spindle  cells,  and  usually  many  blood  vessels. 

Giant  cells  are  most  frequently  seen  in  periosteal  or 
medullary  sarcoma  where  they  represent  the  osteoclasts 
of  developing  bone  or  of  marrow. 

Giant  cells  also  form  in  sarcomatoid  tumors  of  endo- 
thelial origin.  They  are  common  in  the  tumors  called 
perithelioma. 

(c)  Small  round  cell  sarcoma  is  almost  always  de- 
rived from  lymphocytes,  and  is  called  lymphoma  or  lym- 
pho-sarcoma.  Possibly  it  may  at  times  be  of  fibroblastic 
origin. 

(2)   Lymphoma. 

(a)  Simple  lymphoma  is  a  tumor  of  lymph  nodes  in 
which  the  cells  are  of  the  usual  type  of  lymphocytes.  The 
tumor  growth  remains  within  the  distended  capsule  of  the 
node,  the  outlines  of  the  follicles  are  still  partly  preserved,' 
lymph  sinuses  are  not  obliterated,  and  a  reticular  stroma 
is  present.  This  tumor  is  seen  in  pseudo-leukemia,  and 
lymphemia. 

(b)  Lympho- sarcoma  contains  sjnall  and  large  lympho- 
cytes or  larger  cells,  the  outHnes  of  follicles  are  indistin- 
guishable, the  capsules  of  the  nodes  are  infiltrated  and 
ruptured,  and  the  sinuses  obliterated.  Some  of  the  nodes 
in  pseudo-leukemia  and  lymphemia  may  be  of  this  type  but 
the  best  examples  are  seen  as  more  circumscribed  but  very 
malignant  tumors  of  single  groups  of  lymphnodes  or  of 
the  viscera. 


20 


As  one  passes  up  the  scale  of  malignancy  in  lymphoid 
tumors  the  cells  become  larger  and  eventually  fall  in  the 
class  of  large  round  cell  sarcoma. 

( r )  Large  round  cell  sarcoma  must  at  present  be  treated 
as  a  heterogeneous  group,  as  the  origin  of  such  tumors  is 
not  always  clear.  The  group  includes,  (i)  Large  round 
cell  tumors  of  fibroblastic  origin.  (2)  Large  round  cell 
lympho-sarcoma.  (3)  Melano-sarcoma.  In  all  but 
lympho-sarcoma  the  cells  are  apt  to  be  not  strictly  sphe- 
roidal, but  polygonal. 

(1)  Fibroblastic  Large  Round  Celled  Sarcoma. 

Perithelioma  (Telangiectatic  sarcoma),  a  common  tu- 
mor appears  to  be  the  sole  example.  It  is  composed  of  a 
congeries  of  blood  vessels  surrounded  by  thick  sheaths  of 
large  round  or  fusiform  cells.  The  tumor  cells  radiate 
out  from  these  vessels.  Or,  the  vessels  are  lost  and  the 
cells  diffusely  scattered. 

The  exact  origin  of  this  tumor  is  uncertain  but  it 
may  be  regarded  as  a  derivative  of  the  large  epithelioid 
fibroblasts  of  the  sub-endothelial  connective  tissue  of  blood 
vessels. 

(2)  Large  Round  Cell  Lympho-sarcoma. 

These  tumors  are  most  frequently  seen  in  lymph  nodes 
and  in  the  caecum.  They  are  rapidly  growing  and  are 
among  the  most  malignant  of  tumors.  Myeloma,  a  large 
round  cell  tumor  developing  from  certain  cells  of  bone 
marrow,  may  be  classed  here. 

The  structure  includes  the  cells,  and  a  supporting 
framework  of  reticular  connective  tissue,  with  small 
blood  vessels.  The  cells  include  a  small  proportion  of 
lymphocytes,  a  majority  of  large  mononuclear  cells,  and 


In  well  nourished  tumors  the  multiplication  of  cells 
may  be  equally  active  in  all  parts  {central  grozvth). 

Frequently  the  nutrition  is  deficient  in  the  central  parts 
of  a  tumor  and  growth,  is  most  active  or  exclusively  lo- 
cated in  the  peripheral  portions  (peripheral  grozuth). 

Some  tumors  consist  exclusively  of  new  cells  of  a  single 
type,  but  most  new  growths  contain,  besides  the  specific 
tumor  cell,  nerves,  blood  vessels,  and  a  supporting  frame 
work  of  connective  tissue.  In  carcinoma  there  is  often  an 
excessive  amount  of  new  connective  tissue,  usually  as  the 
result  of  productive  infiammation.  The  new  blood  ves- 
sels in  tumors  may  be  the  result  of  productive  inflamma- 
tion, or  the  tumor  cells  when  arising  from  cells  of  ves- 
-sel  walls  may  persist  in  their  normal  functions  and  pro- 
duce many  neoplastic  vessels.  Several  varieties  of  tissue 
arising  from  embryonal  remnants  of  the  same  type  are 
found  in  the  mixed  tumors  or  teratomata. 


Degenerative  Processes. 

Hydropic,  mucoid,  hyaline,  glycogenic,  and  fatty  de- 
generation, are  commonly  observed  in  tumors,  ne- 
crosis is  a  frequent  result  of  imperfect  blood  supply,  and 
inflammatory  processes  occur  as  in  normal  tissues.  These 
changes  tend  to  limit  the  growth  of  tumors  by  diminish- 
ing the  number  of  proliferating  cells.  (Gelatinous  carci- 
noma.) 

The  growth  of  tumors  is  usually  much  more  active 
than  that  of  the  tissue  originating  them.  The  blood  sup- 
ply must  therefore  be  correspondingly  large,  and  indeed 
the  demands  for  nutrition  of  some  tumors  may  cause 
atrophy  of  the  other  tissues  of  the  body.  (Lipoma  in  thin 
subjects;  large  sarcomata.) 


Function  in  Tumor  Tissue. 

Tumor  tissue  usually  retains  some  of  the  function  of 
the  original  tissue;  sometimes  this  function  is  exagger- 
ated in  the  tumor,  and  usually  it  is  perverted  while  not 
inhibited. 

Thus,  the  adenomatous  thyroid  protects  against  the 
myxoedema  which  follow^s  total  extirpation  of  the  thy- 
roid; there  may  be  milk  in  the  cysts  of  adenoma  of  the 
breast,  urine  in  adenomatous  alveoli  of  the  kidney,  bile 
in  metastatic  carcinoma  from  the  liver,  and  many  tumors 
of  mucous  surfaces  secrete  an  excess  of  mucus. 


Metastasis. 

Tumor  cells  wdien  detached  from  one  another  are  still 
more  or  less  capable  of  growing.  Such  detached  cells 
are  often  carried  by  the  lymph  stream,  less  often  by  the 
blood,  to  distant  parts  where  they  lodge  and  develop  into 
metastatic  tumors.  Vascular  tumors  and  those  which 
tend  to  grow  into  lymph  spaces  most  frequently  develop 
metastases  and  are  therefore  most  malignant.  In  many 
tumors  the  paths  and  locations  of  metastases  are  very 
characteristic.  Usually  metastases  are  located  in  the 
nearest  lymph  nodes,  but  sometimes  early  metastases  are 
far  distant  from  the  original  tumor.  (Secondary  growth 
over  scapula  from  cancer  of  stomach.)  Numerous  in- 
stances of  retrograde  metastasis  have  been  recorded.  (In 
pehic  lymph  nodes  from  cancer  of  liver.)  A  favorite 
seat  of  metastasis  for  carcinoma  is  the  bone  marrow. 


Malignancy  of  Tumors. 

Evidences  of  malignancy  may  be  clinical  as  (i)  rapid 
Towth,  (2)  pain  and  ulceration,  (3)  involvement  of  ad- 


jacent  tissues,  (4)  local  recurrence,  (5)  metastases.   (6) 
cachexia. 

Histological  evidences  of  malignancy  include : 

(i)    Markedly  cellular  character. 

(2)  Relatively  large  size  of  cells  and  abundance  of 
chromatin. 

(3)  Abundance  of  mitotic  nuclei. 

(4)  Abnormal  arrangement  of  cells. 

(5)  Tendency  to  invade  neighboring  tissues. 

The  first  three  of  these  histological  features  are  really 
the  means  of  estimating  the  grade  of  anaplasia  which  is 
therefore  the  criterion  of  malignancy.  The  sole  feature 
of  malignancy  of  a  tumor  may  be  an  unfortunate  position 
where  it  endangers  vital  structures,  or  its  large  size, 
or  it  may  be  capable  merely  of  local  recurrence,  or  it  may 
possess  all  the  elements  of  malignancy.  The  prognosis 
varies  in  each  instance.  The  estimation  of  the  malignancy 
of  tumors  requires  an  intimate  knowledge  of  both  their 
clinical  and  their  histological  characters. 


ETIOLOGY  OF  TUMORS. 

(a)  General. 

Age  and  sex  determine  largely  the  types  and  locations 
of  tumors.  There  is  a  very  slight  hereditary  predisposi- 
tion affecting  the  occurrence  and  type  of  tumors. 

(b)  Local. 

Trauma  is  frequently  concerned  with  the  development 
of  tumors,  {epithelioma  of  lip;  sarcoma  after  fractures  of 
hones).  Local  malformations,  as  nsevi  of  the  skin,  mis- 
placed portions  of  adrenal  or  thyroid,  are  frequent  start- 
ing points  of  tumors. 


(c)  Exciting  Cause. 

The  exciting  cause  of  tumor  growth  is  not  known,  and 
several  theories  regarding  its  origin  are  maintained. 

(1)  Cohnheim's  Theory  of  Embryonal  Remnants.  - 

Cohnheiin  beheves  that  tumors  develop  from : 
(i)   Masses  of  complex  or  simple  tissue  misplaced  dur- 
ing embryonal  development,  yielding  the  mixed  tumors 
or  teratomata. 

(2)  Small  groups  of  embryonal  cells,  (a)  misplaced 
or  {b)  not  misplaced,  which  have  failed  to  reach  their 
full  differentiation  into  specific  tissues. 

The  immediate  exciting  cause  of  the  sudden  growth 
of  these  cells  is  increased  nutrition  and  irritation.  Tumors 
therefore  frequently  develop  in  the  breast  and  uterus 
which  pass  through  many  physiological  changes  in  ac- 
tivity. 

Roux  found  1-13  minute  foci  of  cells  misplaced  from 
other  layers  in  the  entoderm  of  frogs'  embryos,  and  Bar- 
furth  produced  dermoids  by  puncturing  ova  in  the  gas- 
trula  stage,  thereby  misplacing  cells. 

In  order  to  elucidate  the  obscure  nature  of  the  in- 
ception of  a  tumor  process  in  these  misplaced  cells,  the 
idea  of  a  disturbance  in  tissue  tension  has  been  suggested. 

The  idea  of  tissue  tension  involves 

(a)  ^Mechanical  pressure  of  cells  on  each  other,  (b)  the 
distribution  of  nutriment  among  the  cells,  and  (c)  the 
acquired  demands  on  the  cells  for  specialized  function 
instead  of  on  their  embryonal  habit  of  simple  multiplica- 
tion. Tissue  growth  normally  ends  when  the  regenerative 
capacities  of  cells  are  restrained  by  tissue  tension.  Em- 
brvonal  remnants  being  cut  out  of  this  circle  of  influ- 
ences are  liable  to  resume  their  embryonal  capacities  of 
multiplication   and   feeling   no   restraint   of   neighboring 


cells  and  no  demands  for  specialized  function  go  to  de- 
velop tumors. 

Scores  of  examples  illustrate  the  partial  truth  of  Cohn- 
heim's  theory :  adrenal  tumors  of  kidney ;  rhabdomyoma 
of  kidney,  genito-urinary  organs,  breast  and  heart ;  em- 
l)ryoid  tumors  of  ovaries,  uterus,  vagina;  adenomyoma  of 
uterus ;  adenoma  of  supernumerary  breast,  thyroglossal 
duct ;  chondroma  of  parotid  from  misplaced  cartilage  from 
the  ear ;  epithelioma  from  branchial  clefts ;  glio-adenoma 
from  misplaced  vertricular  remnants  in  brain ;  choleste- 
atoma of  skull;  osteoma  of  lung;  peritoneal  epithelial 
cysts  in  spleen ;  and  the  entire  group  of  dermoids  and 
teratomata. 

In  fact  in  every  organ  are  well  recognized  types  of 
tumors  certainly  developing  from  embryonal  remnants. 

Such  tumors  producing  a  tissue  differing  from  that  of 
the  harboring  organ  are  called  heterologous. 

Cohnheim's  theory  embodies  one  of  the  great  facts  in 
the  etiology  of  tumors  and  is  very  likely  a  complete  ex- 
planation of  the  group  of  heterologous  tumors. 

It  is  equally  certain  that  all  tumors,  especially  most 
carcinomata,  fibromata,  sarcomata,  of  simple  structure 
homologous  with  that  of  the  harboring  organ,  are  not  de- 
rived from  embryonal  cells.  At  any  rate  there  are  no 
means  of  identifying  such  cells,  in  the  breast  for  instance, 
and  such  a  theory  therefore  appears  not  to  admit  of  proof 
for  all  tumors. 

Ribbert's  Theory. 

Ribbert  endeavors  to  extend  Cohnheim's  principle  to  the 
development  of  tumors  from  groups  of  adult  cells  which 
by  various  means  lose  their  relations  to  their  neighbors 
and  thus  fail  to  feel  the  restraining  effects  of  tissue  ten- 
sion. He  does  not  believe  that  the  development  of  tumors 
requires  any  greater  proliferative  tendencies  than  are  to 


lO 

be  found  in  adult  cells,  which  exhibit  constant  or  intermit- 
tent powers  of  multiplication,  as  in  the  breast  and  uterus 
where  malignant  tumors  are  common.  The  initial  separa- 
tion of  the  cells  from  the  influence  of  the  tissue  tension 
he  refers  to  tlic  grozi'th  of  jiczv  connective  tissue  of  in- 
flammatory origin  into  the  epithelial  layer,  and  he  de- 
scribes such  fibroblasts  between  groups  of  epithelial  cells 
in  psoriasis  of  the  tongue  with  early  epithelioma  and  in 
an  adeno-carcinoma  of  the  stomach. 

This  theory  accords  with  many  facts  known  in  regard 
to  the  origin  of  homologous  tumors ;  with  the  frequent 
development  of  carcinoma  in  chronically  irritated  tissues, 
as  epithelioma  of  muco-cutaneous  junctions,  adenomata  of 
liver  from  ducts  snared  oft  in  cirrhosis;  adenoma  of  kid- 
ney in  old  nephritis ;  epithelioma  following  lupus ;  mul- 
tiple chondromata  of  epiphyseal  lines  in  the  irregular  os- 
sification of  rickets;  carcinomata  after  crushing  injuries; 
syncytioma  from  misplaced  chorionic  cells,  etc. 

It  is  rather  a  matter  of  wonder,  if  one  accepts  this 
theory,  that  tumors  are  not  vastly  more  common,  as  mis- 
placement of  adult  cells  must  be  frequent,  and  Ribbert's 
theory  somewhat  inadequately  defines  the  particular  forces 
precipitating  the  misplaced  cells  into  the  malignant  tumor 
process.  Numerous  very  painstaking  attempts  to  produce 
tumors  experimentally  by  separating  without  destroying 
tissue  cells  have  failed.  Some  other  factor  appears  to  be 
needed. 

The  principles  involved  in  Cohnheim's  and  Rib- 
bert's theories  represent  the  most  mature  judgment  of 
the  problem  of  tumors,  probably  reach  as  near  the  com- 
plete explanation  as  is  at  present  possible,  and  separate  the 
tumor  process  distinctly  from  parasitic  disease. 

Theory  of  Parasitic  Origin  of  Tumors. 

The  possibility  of  a  parasitic  origin  of  tumors  seems 


II 


to  be  inadmissible  for  the  group  of  teratomata  and  it 
may  be  said  that  the  above  considerations  render  unhkely 
such  an  origin  for  the  usual  varieties  of  homologous  tu- 
mors. The  parasitic  theory  is  applied  by  its  adherents 
princi]3ally  to  the  simple  malignant  tumors,  carcinoma  and 
sarconia. 

Are  Microorganisms  Present  in  Tumors? 

I\Iany  observers  have  described  in  the  cells  of  the  grow- 
ing edges  of  carcinoma  and  sarcoma  peculiar  bodies  which 
they  believe  to  be  parasites. 

The  bodies  are  rounded,  homogeneous,  and  refractive, 
in  the  fresh  condition  sometimes  slightly  amoeboid, 
1-15  ,x  in  diameter,  surrounded  by  a  clear  halo  and  some- 
times by  a  membrane,  sometimes  exhibiting  a  nucleus, 
often  showing  bud-like  processes,  in  staining  reaction 
sometimes  acidophile  sometimes  basophile  [Cancer  bodies, 
Plinuiier's  bodies,  Russell's  fuchsin  bodies). 

These  "cancer  bodies"  are  regarded  by  the  adherents 
of  the  parasitic  theory  as  (i)  blastomycetes  or  (2)  pro- 
tozoa; and  by  the  great  majority  of  observers  as  (i) 
cell  inclusions,  of  a  variety  of  types,  but  not  parasitic, 
(2)  centrosomes,  (3)  extruded  nucleoH,  (4)  products 
of  cytoplasmic  or  nuclear  degeneration.  The  great  vari- 
ety of  these  bodies,  their  inconstancy  and  variability  of  oc- 
currence in  tumors,  and  their  presence  in  other  conditions, 
speak  against  their  parasitic  nature. 

Relation  of  Blastomycetes  and  Protozoa  to  Cancer. 

In  a  few  cases  blastomycetes  have  been  cultivated  from 
cancer  but  the  vast  majority  of  attempts  have  failed  and 
most  tumors  appear  not  to  contain  them. 

Attempts  to  produce  timors  by  inoculation  with  blasto- 
mycetes obtained  from  tumors  or  from  other  sources  have 


12 

invariably  failed.  The  results  of  such  inoculations  have 
always  been  purely  inflammatory. 

It  must  be  concluded  therefore  that  although  blasto- 
mycetes  are  occasionally  present  in  cancer  their  presence 
is  accidental  and  they  are  not  the  cause  of  the  disease. 

Protozoa  have  not  been  demonstrated  in  malignant  tu- 
mors, although  it  is  possible  that  some  of  the  bodies  rle- 
scribed  as  such  are  really  protozoa. 

Transplantation  of  Tumors. 

If  tumors  contain  a  parasite  it  is  reasonable  to  expect 
that  the  transplantation  of  a  portion  of  the  growth  from 
one  animal  to  another  of  the  same  species  would  be  suc- 
cessful. Of  many  thousand  such  experiments  only  two 
or  three  have  been  partially  successful,  and  even  in  these 
cases  the  resulting  growth  was  transitory  and^of  doubtful 
nature. 


CLASSIFICATION  OF  TUMORS. 

Tumors  are  classified  in  order  to  display  their  relation 
to  each  other,  and  to  furnish  a  basis  for  uniform  nomen- 
clature. 

At  present  these  objects  are  best  attained  by  naming 
and  classifying  tumors  as  we  name  their  adult  cells  of  ori- 
gin, or  the  tissue  Avhich  the  tumor  most  resembles. 

The  endeavors  to  create  and  introduce  a  classification 
of  tumors  based  on  the  ultimate  embryological  relations 
of  the  originating  cells  have  not  been  successful  and  are 
not  to  be  encouraged.  Embryological  relations  have  much 
influence  in  determining  the  type  and  structure  of  tumors, 
l3Ut  the  habits  of  tumor  cells  are  much  more  often  de- 
termined by  the  late  acquired  habits  of  the  cells  than  by 
their  earlv  embrvoloeical  tendencies. 


29 

tatioii,  producing-  the  papillar}'  cystic  adenomata,  which 
arc  common  in  the  ovary  and  kidney. 

Such  tumors  are  usually  circumscribed  and  peduncu- 
lated, since  the  hyperplasia  may  begin  in  and  be  limited 
to  very  few  alveoli,  possibly  even  to  a  single  alveolus. 
(White.)  Considerable  anaplasia  usually  marks  the  cells 
of  these  tumors,  but  hypersecretion  is  also  common.  The 
membrana  propria  remains  intact,  and  the  supporting  con- 
nective tissue  is  usually  abundant  and  vascular. 

(3)  Malignant  adenoma.  Adenoma  sometimes  proves 
malignant  while  its  structure  rigidly  observes  the  type 
of  simple  adenoma  (e.g.,  adenoma  of  stomach).  Usually 
the  malignant  qualities  of  local  recurrence,  infiltration,  or 
metastasis,  are  associated  with  marked  anaplasia  of  cells, 
which  increase  in  size,  especially  of  the  nuclei,  and  mul- 
tiply rapidly,  increasing  the  depth  of  the  epithelial  lining 
of  the  alveolus.  Such  alveoli  push  their  w^ay  through 
fibrous  or  muscular  tissue,  and  breaking  through  the 
membrana  propria,  they  invade  lymphatics  and  develop 
metastases. 

In  such  metastases  anaplasia  may  increase  or  diminish, 
but  the  strong  tendencies  of  the  cells  to  assume  the  orderly 
alevolar  arrang'ement,  while  exhibiting  the  other  quali- 
tie  of  carcinoma,  justifies  for  many  of  them  the  term 
adeno-carcinoina.  Common  examples  of  malignant  ade- 
noma are  seen  in  the  gastro-intestinal  tract,  and  uterus. 
In  the  ovary  they  are  often  of  the  papillary  cystic  type. 
In  general  it  may  be  said  that  adenoma  of  the  gastro- 
mtestinal  tract  and  uterus  are  usually  malignant. 


3° 


CARCINOMA. 

Definition.  Carcinoma  is  a  malignant  tumor  of  glan- 
dular epithelium. 

Structure.  Carcinoma  is  distinguished  from  adenoma, 
by  the  greater  anaplasia  of  the  cells,  their  more  rapid 
growth,  and  their  failure  to  remain  within  the  confines 
of  a  more  or  less  specialized  membrana  propria. 

It  is  seldom  that  a  carcinoma  maintains  a  uniform 
structure  in  all  its  parts,  or  in  all  stages  of  its  growth. 
Not  only  are  minor  variations  commonly  seen  in  the 
same  growth,  but  frequently  distinctly  different  types  of 
growth  may  be  observed  in  the  different  parts  of  the 
original  tumor,  while  in  metastasis  the  structure  may  be 
totally  at  variance  with  that  of  the  main  tumor. 

Characters  of  Cells. 

In  all  types  of  carcinoma  the  anaplasia  of  the  cells 
is  distinct.  The  cells  are  usually  of  increased  size, 
their  nuclei  show  an  abundance  of  chromatin,  and  mitotic 
figures  are  numerous  in  rapid  cases. 

The  shape  of  the  cells  is  determined  sometimes  by 
their  natural  tendencies,  but  very  often  by  the  local 
conditions  of  nutrition  and  pressure.  The  cells 
show  abnormal  and  usually  diminished  functional  ca- 
pacity. They  are  subject  to  various  degenerations,  fatty, 
hydropic,  mucoid,  hyaline,  glycogenic.  Advanced  mu- 
cinous degeneration  gives  the  tumor  a  swollen,  elastic, 
gelatinous  appearance,  to  which  the  term  gelatinous  car- 
cinoma is  applied.    This  change  tends  to  limit  the  growth. 

The  tumor  exerts  an  irritation  on  the  invaded  tissues 
with  reactive  inflammation  of  exudative  or  productive 
tvpe,  which  tends  partially  to  limit  the  advance  of  the 
growth. 


31 

Sometimes  the  new  fibrous  tissue  is  excessive 
in  amount  and  of  neoplastic  type,  as  in  fibro-carcinoma, 
or  of  acellular  type  as  in  scirrhus.  , 

Mucous  dci^'eneration  of  the  connective  tissue,  if  prom- 
inent, is  designated  by' the  term  myxomatous  carcinoma. 

Carcinomata  of  exposed  surfaces  frequently  ulcerate, 
owing  to  traumatism  of  the  poorly  nourished  tumor  tis- 
sue, and  various  secondary  iniiammations  may  result  from 
infection  by  microorganisms,  including  pyogenic  bacteria, 
bac.  tnhercnlosis,  or  blastomycetes. 

Classification  of  Carcinomata. 

On  general  histological  structure  carcinomata  may  be 
divided  into  three  classes,  adeno-carcinoma,  alveolar  car- 
cinoma, and  diffuse  carcinoma.  While  the  employment 
of  these  terms  may  indicate  the  general  structure  of  a 
carcinoma  and  may  thus  serve  a  useful  purpose,  there 
is  a  growing  tendency  to  name  and  classify  these  and 
other  tumors  according  to  their  exact  cell  of  origin, 
so  far  as  that  can  be  determined,  since  it  appears  that  the 
structure  of  such  accurately  defined  tumors  is  nearly 
always  the  same. 

Varieties. 
(i)  Adeno-carcinoma. 

This  type  of  growth  is  chiefly  seen  in  those  situations 
where  mahgnant  adenoma  occurs,  as  in  the  gastro-intes- 
tinal  and  uterine  mucosae. 

The  cells  are  arranged  in  groups  which  maintain  a 
somewhat  orderly  alveolar  arrangement  and  central  lu- 
men. In  one  variety  the  carcinomatous  process  develops 
extensively  within  the  distended  alveoli  of  papillary  and 
cystic  adenomata. 

Most   adeno-carcinomata   represent  transitional   stages 


33 

between  malignant  adenoma  and  alveolar  or  diffuse  car- 
cinoma. Or  a  tumor  may  begin  as  adeno-carcinoma  and 
maintain  that  type  throughout,  even  in  distant  and  late 
metastases. 

(2)  Alveolar  Carcinoma,  (Medullary.) 

This  is  the  most  frequent  type  of  carcinoma  and  occurs 
in  many  organs,  most  often  in  the  breast. 

The  cells  appear  in  groups  confined  by  the  borders  of 
tissue  spaces,  or  walls  of  vessels,  but  they  are  not  at- 
tached to  these  walls  as  to  a  basement  membrane,  and 
they  do  not  preserve  a  central  lumen. 

(3)  Diffuse  Carcinoma. 

\Mien  the  growth  of  cells  is  very  rapid  and  profuse, 
little  or  no  subdivision  into  orderly  groups  may  exist  and 
the  term  dift'use  carcinoma  may  be  applied.  This  struc- 
ture is  seen  in  many  very  cellular  tumors,  which  are 
rapidly  growing,  very  malignant,  and  never  show^  any 
tendency  to  observe  the  alveolar  arrangement ;  or  the  dif- 
fuse quality  of  the  growth  may  result  from  the  absence 
of  supporting  tissue,  as  in  a  lymph  node  or  blood  vessel ; 
or  there  may  be  a  dift'use  infiltration  of  an  organ  or  tissue 
by  cells  appearing  singly  or  arranged  in  rows,  but  not  in 
alveoli. 


TUMORS  DERIVED  FROM  STRATIFIED 
SQUAMOUS  EPITHELIUM. 

These  growths  form  two  distinct  classes : 
(i)   Epithelial  Papilloma.     (2)   Epithcliojiia. 

(i)   Papilloma. 

Definition.  Epithelial  papilloma  is  a  tumor  in  which 
the  growth  of  epithelium  is  outward  and  papillary  pro- 
jections are  formed  on  the  affected  surface. 

There  are  many  transitional  phases  between  inflamma- 
tory hyperplasia  of  squamous  epithelium  and  neoplastic 
hyperplasia,  which  it  is  difficult  to  distinguish.  The  ve- 
nereal wart  is  an  inflammatory  hyperplasia;  eczema  and 
psoriasis  exhibit  a  uniform  inflammatory  hyperplasia  of 
the  prickle-cell  layer;  while  the  ordinary  wart,  and  the 
papillomas  of  the  bladder  and  larynx  are  examples  of  a 
true  benign  tumor  of  stratified  epitheHum. 

(2)  Epithelioma. 

Definition.  An  epithelioma  is  a  malignant  tumor  de- 
rived from  stratified  squamous  epithelium. 

Origin  and  Structure.  The  tumors  derived  from  the 
so-called  transitional  epithelium,  as  in  the  bladder,  are 
included  in  this  class.    All  epitheliomata  are  derived  from 


34 

the  deeper  layers  of  cells,  but  while  in  some  {acaiithonia- 
ta),  the  cells  assume  the  pavement  type,  in  others  they 
never  progress  in  their  natural  development,  but  remain 
small  and  fail  to  exhibit  the  pavement  type,  or  develop 
prickles,  or  hornification. 

There  are  several  inflammatory  conditions  character- 
ized by  a  simple  hypertrophy  of  the  basal  layers  of  strati- 
fied squamous  epithelium,  as  in  eczema  and  psoriasis,  and 
sometimes  hypertrophied  papillae  project  distinctly  into 
the  connective  tissue,  but  in  epithelioma  the  growth  of 
cells  is  more  active  and  there  is  progressive  invasion  of 
the  derma  or  submucosa  by  masses  of  cells  of  neoplastic 
type. 

The  variety  of  structure  in  tumors  of  stratified  squa- 
mous epithelium  is  very  extensive  and  depends  upon  (i) 
the  particular  cell  form  giving  origin  to  the  tumor,  and 
(2)  the  grade  of  anaplasia  of  the  cells.  No  other  tissue  is 
capable  of  yielding  such  a  multiplicity  of  tumor-cell 
forms. 

Varieties . 

(i)   Prickle -cell  Epithelioma.     (Acanthoma.) 

In  one  very  distinct  class  of  epithelioma  the  cells  are 
derived  from  the  prickle-cell  layer,  and  they  retain  their 
original  flat  pavement  character,  with  prickles,  and  ten- 
dency to  hornification. 

In  such  tumors  the  prickle  cells  are  readily  identified, 
the  pavement  tendencies  give  rise  to  concentric  masses 
of  cells,  often  with  hornified  centres,  called  epithelial 
"pearls." 

Such  tumors  frequently  develop  in  the  skin,  at 
muco-cutaneous  junctions,  and  in  mucous  membranes, 
and  they  constitute  the  most  numerous  class  of  epitheli- 
oma. Their  malignancy  depends  on  their  situation  and 
degree  of  anaplasia.     In  the  skin  they  are  less  malignant 


35 

than  in  the  mucous  membranes,  but  all  are  characterized 
by  tendency  to  local  recurrence,  early  ulceration,  and 
metastasis  in  the  lymph  nodes. 

In  the  metastases  the  same  histological  characters  are 
usually  maintained,  but  the  prickles  are  the  first  features 
to  be  lost.  Occasionally,  in  the  original  growth  the 
prickles  are  partly  lost,  the  cell  bodies  become  more  gran- 
ular, the  cells  are  arranged  in  narrow  anastomosing  cords, 
and  the  term  tubular  cpithcUouia  is  sometimes  applied. 

(2)  Reticulated  Epithelioma. 

This  tumor  occurs  in  the  skin,  in  two  rather  distinct 
forms.  ( i)  The  cells  are  small,  cuboidal  or  fusiform,  and 
densely  packed  in  small  or  larger  masses  in  the  lymph 
spaces  of  the  derma.  These  masses  are  connected  by 
thinner  cords  of  cells,  giving  to  the  growth  on  section  a 
peculiar  reticulated  appearance.  Rodent  ulcer  is  such  a 
reticulated  epithelioma  with  large  compact  masses  of  cells 
and  usually  with  ulceration  of  the  surface. 

The  above  masses  of  cells  may  undergo  lique- 
faction in  one  of  several  foci,  with  dilatation  of  in- 
closed spaces.  An  alveolar  appearance  is  thus  formed  and 
the  tumor  is  called  adenoid  cystic  epithelioma. 

These  tumors  possess  only  slight  malignancy,  very  sel- 
dom involving  adjacent  lymph  nodes. 

(3)  Papillary  and  Flexiform  Epithelioma. 

A  frequent  form  of  epithelioma  arising  from  mucous 
surfaces  is  composed  of  thick  convoluted  layers  of  epithe- 
lium irregularly  twisted  and  supported  by  a  variable 
amount  of  connective  tissue.  Sometimes  this  connective 
tissue  is  abundant,  in  which  case  the  identity  of  the 
convoluted  layers  of  epithelium  is  distinct.  Sometimes 
the  connective  tissue  is  reduced  to  a  verv  thin  coverino- 


3<i 

of  blood  vessels  and  nearly  the  entire  bulk  of  the 
tumor  is  composed  of  a  more  or  less  diffuse  mass  of 
epithelial  cells  in  which  run  numerous  thin  walled 
blood  vessels.  In  either  case  the  cells  usually  lack 
prickles,  always  fail  to  show  hornification,  and  frequently 
become  compressed  into  fusiform  shapes. 

These  tumors  show  marked  local  malignancy  and  cause 
wide  metastasis. 

(4)  Epithelioma  of  Atypcal  Cell  Type. 

In  a  considerable  number  of  tumors  arising  from  squa- 
mous epithelium  there  is  extreme  anaplasia  of  the  cells, 
which  combined  with  the  local  effects  of  pressure,  produce 
very  atypical  cell  forms.  In  these  tumors  the  cells  always 
lack  prickles  and  hornification.  They  are  usually  short 
and  fusiform,  but  they  may  become  considerably  elon- 
gated. They  are  usually  packed  side  by  side,  in  dense 
masses.  They  are  usually  well  separated  from  the  sur- 
rounding connective  tissue,  if  that  tissue  is  adult,  but  if  it 
is  oedematous  or  cellular  the  epithelial  cells  may  pass  in- 
sensibly into  the  connective  tissue. 

In  the  metastases  of  these  tumors  the  fusiform  shape 
may  reappear  or  the  cells  may  revert  to  the  large  pave- 
ment type. 

The  melanoma  of  epithelial  origin  illustrates  all  of  these 
phases,  and  the  epithelioma  of  the  cervix  uteri  may  exhibit 
many  of  them. 

Syncytioma  Malignum.     Deciduoma. 

Definition.  Syncytioma  is  a  malignant  tumor  arising 
from  the  epithelium  of  the  chorionic  villi. 

Structure.  The  chorionic  epithelium  is  composed  of  two 
layers:  (i)  an  outer  mass  of  fused  cell  protoplasm  with 


21 


occasionally  some  oiant  cells.     Hemorrhag-e,  necrosis,  ul- 
ceration, and  metastasis  are  common. 

(3)  Melanoma.  It  is  sometimes  difficult  to  distinguish 
individual  examples  of  rOund  cell  tumors  of  endothelial  or 
epithelial  origin,  from  large  round  cell  sarcoma.  This  dif- 
ficulty is  encountered  in  the  group  called  true  melano- 
sarcoma.  These  tumors  arise  in  the  skin  and  choroid,  may 
long  remain  more  or  less  quiescent,  and  may  suddenly, 
as  after  incomplete  removal,  exhibit  rapid  growth  and 
v^^idespread  metastasis. 

Two  views  are  held  regarding  their  origin :  ( i )  They 
are  all  epitheliomas  derived  from  the  downward  growth 
of  palisade  cells  of  the  Malpighian  layer  (Unna)  ;  or,  (2) 
they  are  all  endotheliomata  derived  from  the  lining  cells 
of  minute  capillaries  or  lymph  spaces  of  the  rete.  Many 
of  them  are  certainly  epitheliomata,  and  some  are  prob- 
ably endotheliomata.  These  conflicting  views  have  led 
some  to  use  the  term  melanoma. 

The  pigment  is  developed  by  large  branching  cells, 
chromatophores,  which  accompany  the  metastases. 


ENDOTHELIOMA. 


Definition.  A  tumor  developing  from  the  lining  cells 
of  lymph  or  blood  vessels  or  of  serous  surfaces. 

Structure.  It  is  usually  cellular,  and  the  cells  long  re- 
tain their  endothelial  characters,  with  vesicular  nuclei,  nu- 
cleoli, homogeneous  cytoplasm,  and  condensed  cell-bor- 
ders. They  may  form  pearls,  sometimes  with  calcified 
centres.    Endothelial  cells  are  less  sharply  separated  from 


22 


supporting  connective  tissue  than  are  epithelial  cells. 
Their  relation  to  fibroblasts  is  seen  in  the  frequent  trans- 
formation of  endothelial  tumors  into  fibrous  growths, 
less  frequently  into  mucous,  or,  possibly,  cartilaginous  tis- 
sue. 

Histological  varieties  are  very  numerous. 

(i)  Perivascular  Endothelioma. 

This  type  is  seen  principally  in  slowly  growing  multiple 
timiors  of  the  dura  mater.  The  cells  are  spindle  shaped 
with  rather  homogeneous  cytoplasm  and  dense  cell  bor- 
ders. The  imit  of  the  tumor  is  a  small  blood  vessel  sur- 
rounded by  10-15  concentric  layers  of  these  cells. 

Common  variations  of  this  tumor  are,  diffuse  growth  of 
spindle  cells  resembling  fibro-sarcoma,  hyaline  transfor- 
mation of  considerable  areas,  and  calcification  of  small 
foci  of  cells  (endothelial  pearls,  psainmoiiia) . 

(2)  Interfascicular  Endothelioma. 

This  tumor  occurs  in  the  parotid  and  other  glands, 
and  in  the  derma.  It  is  derived  from  a  multiplication 
of  the  lining  cells  of  lymph  spaces,  and  in  the  early  stages 
the  lumen  of  the  space  remains  pervious.  Or  the  cells 
continue  to  proliferate  and  close  the  lumen.  The  inter- 
vening stroma  often  undergoes  hyaline  degeneration  pro- 
ducing a  peculiar  appearance  sometimes  designated  as 
cylindroma.  Or  the  tumor  may  combine  with  proliferat- 
ing fibroblasts  to  produce  cartilage.  (Chondro-endothel- 
ioma.) 

("3)  Alyeolar  Endothelioma. 

When  the  proliferating  cells  of  lymph  spaces  multiply 
extensively,  a  cellular  tumor  results  composed  of  groups 
of  cells  in  alveolar  arrangement  supported  by  thin  bands 


of  connective  tissue  resembling,  the  membrana  propria 
of  glands. 

Such  tumors  are  seen  in  the  parotid,  antrum  of  High- 
more,  kidney,  ovary,  etc. 

The  central  lumen  may  persist  or  in  the  masses  of 
cells  small  secondary  lumina  or  spaces  form  filled  with 
mucus  or  other  fluids.  The  cells  may  retain  the  char- 
acters of  endothelia  or  may  be  small  and  cuboidal  or  be- 
come distinctly  columnar. 

(4)  Angeio-endothelioma.     (''Angeio- sarcoma.") 

In  this  type  the  cells  of  blood  or  lymph  vessels  multiply 
while  the  lumen  of  the  vessel  and  its  circulating  contents 
are  fully  maintained,  yielding  vascular  tumors  of  which 
the  unit  is  a  vessel  walled  by  two  or  more  rows  of  cuboidal 
endothelial  cells. 

Sometimes  the  vessel  is  lined  by  very  numerous  paral- 
lel rows  of  cells.  Sometimes  the  lumen  is  dilated,  and 
the  tumor  resembles  papillary  epithehoma  (endothelioma 
of  bone).  In  these  tumors  there  is  little  growth  of  con- 
nective tissue. 

(5)  Endothelioma  of  Serous  Membranes. 

This  tumor  is  most  common  in  the  pleura,  where  it 
mav  develop  considerable  bulk  of  new  fragile  tissue  dis- 
tending the  pleural  cavity  or  it  may  invade  the  lung 
through  lymph  vessels.  The  superficial  growths,  even 
when  of  large  bulk,  exhibit  a  large  alveolar  structure  with 
cuboidal  or  columnar  cells  and  little  mterstitial  tissue. 

When  invading  the  lung  the  cells  appear  in  groups  dis- 
tending the  tissue  spaces  and  recalling  the  structure. of 


carcinoma. 


Endothelioma  of  the  peritoneum  is  very  rare.  It  is 
composed  of  large  flat  cells  which  tend  to  retain  their  en- 
dothehal  characters  in  secondary  and  metastatic  grow^ths. 


24 

MYOMA. 

Definition.     A  myoma  is  a  tumor  of  muscle  tissue. 
Structure.     These  tumors  are  of  two  varieties : 

(i)   Leiomyoma,  composed  of  smootti  muscle  cells. 

(2)  Rhabdomyoma,  .composed  of  striated  muscle  cells. 
Both  varieties   contain   also   a   supporting   framework 

of  connective  tissue  often  of  neoplastic  type,  and  blood 
vessels. 

(i)  Leiomyoma.  The  commonest  example  of  this  tu- 
mor is  the  uterine  fibro-myoma.  It  is  seen  also  in  the 
intestinal  wall,  and  viscera,  and  is  often  multiple.  The 
cells  are  long  spindles  with  long  oval  nuclei.  They 
may  be  distinguished  from  fibroblastic  tumor  cells  by  ( i ) 
their  greater  affinity  for  eosin  and  (2)  the  presence  of 
nuclei  within  the  fibres  on  cross  section;  while  (3)  their 
arrangement  in  fascicles  is  characteristic. 

(3)  Rhabdomyoma  is  a  rare  tumor  seen  in  the  breast, 
heart,  or  genito-urinary  organs.  The  cells  vary  greatly  in 
size  and  development,  but  are  identified  by  their  cross 
striation.  Rhabdomyoma  is  usually  a  mixed  tumor,  ter- 
atoma, and  contains  several  varieties  of  tissue.  It  may 
exhibit  local  recurrence  after  removal  but  seldom  any 
other  grade  of  malignancy. 


TUMORS   OF    NERVE-TISSUE. 

Definition.    There  are  two  varieties : 

(i)  Ganglionic  or  true  Neuroma  is  composed  of  gan- 
glion cells  and  their  fibres,  and  glia  cells.  (2)  Glioma  is 
composed  of  glia  cells. 


25 

structure.  (i)  Ganglionic  neuromata  occur  in  the 
brain  and  in  various  mixed  tumors  (teratomata)  of  the 
ovary,  testis,  sacral  region,  and  adrenal.  They  are  iden- 
tified on  the  presence  of  poorly  developed  ganglion  cells 
supported  by  glia  and  nerve  fibres,  and  blood  vessels. 
They  are  rare. 

(2)  Glioma  is  common  in  the  brain.  It  is  composed 
of  glia  cells  with  many  hair-like  processes.  Blood  ves- 
sels are  numerous  and  hemorrhages  common. 

In  the  retinal  gHoma  the  cells  are  very  numerous,  pro- 
cesses deficient,  and  the  tumor  somewhat  resembles 
lympho-sarcoma. 

False  Neuroma  is  a  term  applied  to  certain  tumors  de- 
veloping in  nerve  trunks.  They  are  usually  multiple  and 
often  as  cellular  as  sarcoma,  and  are  found  in  the  skin  or 
along  peripheral  nerve  trunks.  In  the  early  stages  the 
cells  are  large  flat  endothelia,  later  they  become  fusiform 
and  resemble  fibroblasts,  and  by  regressive  changes  the 
tumor  may  become  largely  fibrous.  The  arrangement  of 
the  cells  in  whorls  is  characteristic. 


ANQEIOMA, 


Definition.  Angeioma  is  a  tumor  composed  largely  of 
blood  vessels  (Hemangeioma)  or  lymph  vessels  (Lymph- 
angeioma). 

(i)  Hemangeioma.  {a)  Simple  Angeioma.  This  is  a 
common  tumor  of  the  skin,  where  it  is  called  vascular 
ncu'Z'us.  It  occurs  less  frequently  in  mucous  membranes 
and  bone,  and  it  sometimes  involves  all  the  soft  tissues  of 
an  entire  extremity,  especially  in  young  children. 


26 


It  consists  of  a  congeries  of  small  or  capillary  blood 
vessels,  preexisting  or  new  formed,  whose  walls  usually 
contain  an  excess  of  endothelia  and  fibroblasts,  while  the 
supporting  connective  tissue  is  also  cellular.  There  are 
numerous  gradations  up  to  angeio-endothelioma,  and  one 
of  these  in  which  the  new  vessels  are  very  numerous^  and 
of  small  size'  with  excess  of  endothelia  is  called  angioma 
si  in  pi  ex  hypertrophicnin. 

(b)  Cavernous  angeioma  occurs  in  the  skii;  or  viscera, 
and  is  composed  of  circumscribed  masses  of  widely  dilated 
blood  spaces  supported  by  trabeculse  of  connective  tissue. 

(2)  Lymphangeioma  is  a  tumor,  usually  congenital, 
sometimes  acquired,  composed  of  dilated  lymph  chan- 
nels, supported  by  thin  fibrous  or  fibro-muscular  walls.  It 
occurs  in  the  skin,  tongue  (niacroglossia) ,  and  subserous 
tissues.  The  contents  of  the  lymph  spaces  are  clear  and 
watery  or  milky.  Keloid  is  a  fibro-lymphangeioma  of  the 
skin.  Lymph  scrotum  is  a  mechanical  or  inflammatory 
dilatation  of  the  lymphatics  of  the  scrotum,  seen  in  filaria- 
sis,  and  is  a  result  of  occlusion  of  lymphatics  by  scars. 


ADENOMA. 

Definition.  Adenoma  is  a  tumor  composed  of  glandular 
epithelial  cells  maintained  more  or  less  perfectly  in  the 
form  of  alveoli,  with  basement  membranes  and  cen- 
tral lumina. 

Structure.  The  unit  of  this  tumor  is  to  be  regarded 
as  the  alveolus  rather  than  the  epithelial  cell,  although 
the  neoplastic  process  resides  in  the  lining  cells. 


27 

The  multiplication  of  epithelial  cells  increases  the 
length,  sometimes  the  depth  of  the  lining,  and  frequently 
the  lumen  of  the  affected  alveolus,  all  of  which  changes 
cause  a  greater  number  of  sections  of  alveoli  to  appear 
in  the  field.  Usually  lateral  sprouts  early  develop  from 
the  original  alveolus,  producing  new  alveoli,  or  new  al- 
veoli develop  from  the  downward  growth  of  proliferating 
surface  epithelium.  In  papillary  and  cystic  adenoma  there 
may,  however,  be  no  new  alveoli  formed,  while  lateral 
pouches  may  develop  in  inflammatory  glandular  hyperpla- 
sia. The  essential  process  in  adenoma  must  therefore  be 
regarded  as  the  neoplastic  hyperplasia  of  the  epithelial 
cells. 

Alveoli  which  are  elongated  and  pouched  become 
variously  twisted,  producing  circumscribed  tumors  dif- 
fering slightly  in  structure  from  the  normal  gland.  (Sim- 
ple adenoma.) 

Alveoli  which  are  widened,  principally  by  the  excessive 
growth  of  epithelium  into  the  lumen,  and  by  retained  se- 
cretion, produce  the  papillary  adenoma  and  the  cystic 
adenoma. 

Alveoli  in  which  the  depth  of  cells  is  much  increased 
produce  as  a  rule  rather  malignant  growths  capable  of  in- 
filtrating surrounding  tissues  and  called  malignant 
adenoma  {adenoma  destruens). 

Adenomatoid  Inflammatory  Hyperplasia. 

In  mucous  membranes  which  are  the  seat  of  chronic 
catarrhal  inflammation  there  is  frequently  a  development 
of  stroma  and  especially  of  glandular  alveoli  which  it  is 
very  difficult  to  distinguish  from  true  adenoma  by  either 
gross  or  microscopical  examination. 

Unquestionably  some  of  these  inflammatory  hyperpla- 
sias pass  into  true  progressive  neoplasms  but  others  dis- 


28 

appear  when  the  irritation  causing  them  is  removed.  It 
is  of  prognostic  importance  to  distinguish  such  conditions 
from  tumors.  The  inflammatory  hyperplasias  usually  ex- 
hibit little  or  no  anaplasia  but,  rather,  metaplasia  of  cells, 
i.e.,  columnar  cells  change  to  cuboidal,  or  cuboidal  to 
squamous,  but  they  fail  to  show  the  abundance  of  nu- 
clear chromatin  seen  in  tumor  cells;  their  arrangement  is 
more  orderly  than  in  adenoma,  although  it  is  claimed  that 
papillary  projections  may  develop;  the  process  is  less  cir- 
cumscribed than  is  usual  with  adenoma ;  there  is  usually 
a  recognizable  inflammatory  hyperplasia  of  the  stroma; 
and,  clinically,  a  removal  of  the  irritant  is  followed  by 
subsidence  of  the  hyperplasia.  These  conditions  occur 
principally  in  the  nares,  uterus,  rectum,  and  prostate. 

( 1 )  Simple  adenoma.  This  is  a  common  tumor  of  the 
breast,  ovary,  liver,  kidney,  and  mucous  membranes.  It 
is  usually  circumscribed  and  often  polypoid.  The  cells 
show  slight  anaplasia,  but  are  often  smaller  and  more 
numerous  than  in  the  normal  alveolus. 

They  commonly  retain  much  of  their  original  function. 
The  membrana  propria  is  intact,  vessels  and  nerves  are 
sufflciently  provided,  and  the  supporting  connective  tissue 
is  normal,  or  if  excessive,  the  tumor  is  called  iibvo-aden- 
ouia.  Lateral  pouches  sometimes  develop  from  the 
elongating  alveoli,  especially  when  the  lumen  is  moder- 
ately widened  (tubular  adcuouia). 

(2)  Papillary  adenoma.  An  excessive  growth  of  epi- 
thelium may  lead  to  a  protrusion  of  the  epithelial  layer 
into  the  lumen,  followed  or  not  by  vascular  connective 
tissue  papillae.  Dichotomous  branching  of  these  papillae 
may  lead  to  extreme  dilatations,  and  complex  figures  on 
section.     Retention  of  secretion  commonlv  aids  the  dila- 


n 

multiple  nuclei,  which  possesses  ameboid  properties  {the 
syncytium),  and  (2)  an  inner  layer  of  small  cuboidal  cells 
(  I.an'^hans'  layer). 

Both  layers,  but  especially  the  syncytium,  are  concerned 
in   the  tumor. 

The  cells  of  the  tumor  are  mostly  large  protoplasmic 
masses  with  numerous  nuclei,,  possessing  ameboid  proper- 
ties, and  accompanied  by  a  smaller  number  of  cuboidal 
cells.  These  cells  often  surround  new  blood  sinuses  and 
exhibit  a  special  tendency  to  invade  the  lymph  or  blood 
vessels  of  the  uterine  wall,  through  which  widespread 
metastases  rapidly  develop.  The  tumors  first  appear  as 
multiple,  circumscribed,  soft,  bleeding  outgrowths  on  the 
uterine  mucosa,  or  as  a  diffuse  infiltration  of  the  uterine 
wall.     They  frequently  develop  from  hydatid  moles. 


TUMORS  OF  COMPLEX  ORIGIN. 

Many  of  the  sarcomata  and  endotheliomata  show  more 
than  one  type  of  tissue,  as  indicated  by  the  terms  chondro- 
sarcoma, osteo-sarcoma,  lipo-sarcoma,  chondro-endotheli- 
oma-  These  tumors  illustrate  the  ordinary  metaplasia  of 
such  cells  and  are  not  included  in  the  group  of  tumors  of 
complex  nature. 

Definition.  When  a  tumor  exhibits  two  or  more  vari- 
eties of  tissue  not  closely  related  genetically  or  in  struc- 
ture, it  Is  called  a  complex  tumor. 

Such  neoplasms  result  from  misplaced  complex  masses 
of  embryonal  tissue. 


38 

Varieties. 

There  are  two  classes,  (i)  The  Dermoid,  and  (2) 
The  Teratoma. 

(  I )   The  Dermoid, 

Dermoids  are  complex  tumors  composed  of  skin  and 
its  appendages.  These  tumors  are  seen  chiefly  in  the 
ovary,  testicle,  brain,  and  orbit.  They  are  usually  cystic. 
The  ovarian  dermoids  are  lined  by  stratified  squamous 
epithelium  from  which  develop  hair  and  teeth,  while  the 
cyst  is  filled  with  sebaceous  material  and  epithelial  scales. 

(2)  The  Teratoma. 

A  teratoma  is  a  complex  tumor  exhibiting  a  greater 
variety  of  tissues  than  the  dermoid,  including  skin  and  its 
appendages,  glands,  fat,  muscle,  nerves,  and  often  con- 
siderable portions  of  organs, .as  the  intestine,  and  central 
nervous  system. 

There  appear  to  be  many  gradations  between  the  ter- 
atoma and  the  higher  distinct  parasitism  of  one  embryonic 
foetus  in  another.  Teratomata  are  most  frequent  in  the 
sacral  region,  uterus,  and  testicle. 


RO(»e-»flTTDI 


Date  Due 

'% 

OCT 

1  2  1945 

/ 

: 

! 

f) 

1 

Rl)65l 


Ew52 


/  I      Ewing 

Syllabusjtiectures  oa  tumors 


COLUMBIA  UNIVERSITY  LIBRARIES  (hsi.stx) 

RD  651  Ew52  C.1 

Syllabus  of  lectures  on  tumors. 


2002266393 


■;viV7-^;? 


